Cholesterol Efflux Capacity Improves Atherosclerotic CVD Risk Prediction

Cholesterol efflux capacity remained inversely associated with incident atherosclerotic cardiovascular disease without attenuation in an adjusted model.

Cholesterol efflux capacity (CEC) appears to improve atherosclerotic cardiovascular disease (ASCVD) risk prediction—beyond what coronary artery calcium (CAC), family history, and high-sensitivity C-reactive protein (hs-CRP) can provide, according to data published in the Journal of the American College of Cardiology.

As the study authors pointed out, low high-density lipoprotein cholesterol (HDL-C) is considered an important risk factor for ASCVD, but that association may be attenuated.

They enrolled 1972 individuals (mean age: 44 ± 9.2 years; 44% men; 47% African Americans) who were part of the Dallas Heart Study. Fifty-two percent of patients had prevalent CAC. Family history and “premature” family history were also reported in 31% and 10%, respectively, as well as hs-CRP >2 mg/l in 58% of patients.

The primary end point was a composite of first nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]), or death from CV causes. Nonfatal end points were ascertained and adjudicated by 2 cardiologists who were unaware of the CEC measurements.

A first ASCVD event occurred in 97 patients, which included 28 MIs, 32 strokes, 5 CABGs, 11 PCIs, and 21 CV deaths during a median 9.4 years of follow-up (95% confidence interval [CI]: 9.0-9.8). A decreased risk of ASCVD was observed in those patients with CEC more than the median vs less than the median (3.1% vs 6.7%; P=.0003).

In patients with prevalent CAC (n=1030), those with CEC more than the median vs less than the median also had a decreased risk of ASCVD (5.4% vs 10.5%; P=.003). Patients with family history and elevated hs-CRP saw similar results (5.8% vs 10%; P=.05 and 3.8% vs 7.9%; P=.004, respectively).

CEC remained inversely associated with incident ASCVD without attenuation in a fully adjusted model that accounted for all traditional risk factors, prevalent CAC, family history, elevated hs-CRP (adjusted hazard ratio [HR]: 0.35; 95% CI: 0.23-0.55).

“The ability of CEC to improve risk prediction beyond using CAC, FH [family history], and hs-CRP was assessed using metrics of calibration, discrimination, and reclassification,” researchers wrote. “CEC more than the median vs less than the median improved discrimination indexes as determined by the c-statistic and IDI [integrated discrimination improvement] when added to risk factor-adjusted models, including either prevalent CAC, FH, or elevated hs-CRP.”

They concluded, “Among low-risk individuals, efflux adds to ASCVD risk prediction beyond using CAC, FH, and hs-CRP, which are 3 well-validated and clinically used markers.”

In the future, if standardized assays are developed, CEC may serve as a surrogate marker for evaluating novel therapeutic strategies.


Mody P, Joshi PH, Khera M, Ayers CR, Rohatgi A, et al. Beyond coronary calcification, family history, and C-reactive protein. Cholesterol efflux capacity and cardiovascular risk prediction. J Am Coll Cardiol. 2016;67(21):2480-2487. doi: 10.1016.j.jacc.2016.03.538.